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A key factor leading to impaired immunity in HIV infection is an alteration of the pattern of cytokine response, although its precise nature remains controversial, particularly the in vivo influence of HIV on interleukin (IL)-12 synthesis.

The study was conducted in Bobo-Dioulasso, Burkina Faso, where Mycobacterium tuberculosis infection and human immunodeficiency virus type 1 (HIV-1) infection are prevalent.To identify proportions of representative (test) populations who are reactive to the tuberculin skin test, and to study the relationship between CD4 T-lymphocyte counts and the induration size of the tuberculin skin test in these groups.A group of 435 healthy students was tuberculin skin tested in order to evaluate the intensity of skin testing in a 'normal' population. The study group consisted of 195 subjects with or without tuberculosis, and with or without HIV-1 infection, who received a tuberculin skin test and a CD4 T lymphocyte count on the same day.In total, 90% of the control (nontuberculous, HIV negative) subjects, 32% of the HIV-1 seropositive subjects, 76.5% of the tuberculous patients and 57% of the tuberculous HIV-1 seropositive patients were tuberculin positive. There was no direct correlation between the induration size of reactions to the tuberculin skin test and CD4 T-lymphocyte count in these study groups using linear regression analysis.In vivo skin testing using tuberculin yields clinically significant information on the degree of immunodeficiency which is different from that of CD4 T-lymphocyte counts. The tuberculin skin test should therefore be used as an independent marker of the weakened immunological status of HIV-1 seropositive subjects.

To gain new insights on the origin, evolution, and modes of dissemination of human T-cell leukemia virus type 1 (HTLV-1), we performed a molecular analysis of 58 new African HTLV-1 strains (18 from West Africa, 36 from Central Africa, and 4 from South Africa) originating from 13 countries. Of particular interest were eight strains from Pygmies of remote areas of Cameroon and the Central African Republic (CAR), considered to be the oldest inhabitants of these regions. Eight long-term activated T-cell lines producing HTLV-1 gag and env antigens were established from peripheral blood mononuclear cell cultures of HTLV-1 seropositive individuals, including three from Pygmies. A fragment of the env gene encompassing most of the gp21 transmembrane region was sequenced for the 58 new strains, while the complete long terminal repeat (LTR) region was sequenced for 9 strains, including 4 from Pygmies. Comparative sequence analyses and phylogenetic studies performed on both the env and LTR regions by the neighbor-joining and DNA parsimony methods demonstrated that all 22 strains from West and South Africa belong to the widespread cosmopolitan subtype (also called HTLV-1 subtype A). Within or alongside the previously described Zairian cluster (HTLV-1 subtype B), we discovered a number of new HTLV-1 variants forming different subgroups corresponding mainly to the geographical origins of the infected persons, Cameroon, Gabon, and Zaire. Six of the eight Pygmy strains clustered together within this Central African subtype, suggesting a common origin. Furthermore, three new strains (two originating from Pygmies from Cameroon and the CAR, respectively, and one from a Gabonese individual) were particularly divergent and formed a distinct new phylogenetic cluster, characterized by specific mutations and occupying in most analyses a unique phylogenetic position between the large Central African genotype and the Melanesian subtype... (D'après résumé d'auteur)

Pendant et à la suite de l'épidémie de fièvre de la Vallée du Rift dans le sud mauritanien, nous avons réalisé plusieurs enquêtes épidémiologiques pour déterminer l'aire d'extension de l'épizootie et de l'épidémie. Nous avons pu définir 2 aires épidémiques, centrées l'une autour de Rosso, sur la rive droite du Sénégal et l'autre à proximité de la ville de Kaédi. L'aire d'épizootie débordait sur la rive gauche du fleuve, entre Rosso et Saint-Louis. Plusieurs facteurs écologiques nouveaux ont pu jouer un rôle dans la genèse et l'entretien de l'épizootie et de l'épidémie : la mise en eau de barrages sur le fleuve pour l'irrigation et une pluviométrie plus abondante que précédemment. (Résumé d'auteur)

Chimpanzees are one of the few species, along with humans, susceptible to persistent HIV-1 infection. However, HIV-infected chimpanzees do not exhibit the marked immune system alterations seen in humans and remain relatively resistant to AIDS. In humans, HIV infection leads to unresponsiveness of T cells in response to TCR stimulation, associated with increased T cell death by apoptosis. In an effort to understand some of the mechanisms used to limit lentivirus infection in African nonhuman primates, we compared apoptosis in infected humans vs chimpanzees in CD4 and CD8 T cells in relation with the expression of Bcl-2 and Fas molecules. The intensity of apoptosis in CD4 and CD8 T cells from infected chimpanzees was very low, was not inducible by several TCR-dependent activators, and was comparable to that detected in noninfected chimpanzees. Moreover, CD45RO+ and HLA-DR+ subsets, which were shown to exhibit ex vivo a high propensity to undergo apoptosis in infected humans, were not modified in infected chimpanzees. Interestingly, in contrast to the situation found in infected humans, Fas ligation by agonistic Abs or recombinant human Fas ligand on CD4 and CD8 T cells from infected chimpanzees did not induce apoptosis in these subsets even when Bcl-2 was down-regulated. Finally, this resistance to apoptosis was associated with the predominance of CD3 T cells with a Th1 phenotype. Together these observations argue for a strong relationship among the absence of chronic immune stimulation in HIV-1-infected chimpanzees, the normal control of lymphocyte survival, and the resistance to disease progression.

HIV infection is marked by the progressive destruction of the CD4 T lymphocyte subset, an essential component of the immune system and a vital source of cytokines required for differentiation of natural killer (NK) and gamma delta T cells, for maturation of B lymphocytes into plasmocytes, and for differentiation of CD8+ T cells into virus-specific cytotoxic T lymphocytes. CD4 T lymphocytes are also a source of chemokines which control migration of lymphocytes to the site of infection and which also inhibit HIV entry into CD4-expressing targets. Continuous production of viral proteins leads to an unbalanced immune activation and to the triggering of apoptotic programs, turning mononuclear cells, including CD4 T cells, CD8 T cells and APC, into effectors of apoptosis, leading to fratricidal destruction of healthy uninfected cells expressing the death receptors. Inappropriate PCD is also responsible for the disappearance of T helper cells primed for type-1 cytokine synthesis, thus contributing to the lack of survival factors which could prevent spontaneous lymphocyte apoptosis. Under potent anti-retroviral therapies, a significant decrease in spontaneous, TCR- and CD95-induced lymphocyte apoptosis is observed, concomitant with a partial quantitative and qualitative restoration of the immune system in treated patients. However, owing to the suppressive effect of anti-retroviral drugs on physiological apoptosis, these therapies are associated with alteration of TNF-alpha-regulated T cell homeostasis, leading to an accumulation in the blood of T cells primed for TNF-alpha synthesis, and contributing to the development of a new syndrome associated with these treatments, the lipodystrophy syndrome.