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A remarkable feature of the adaptive immune system is the speed at which small numbers of antigen-specific lymphocytes can mediate a successful immune response. Rapid expansion of T and B lymphocyte clones that have receptors specific for a particular antigen is one of the primary means by which a swift response is generated. Although much of this clonal expansion is caused by the division of antigen-specific cells, here we demonstrate an additional mechanism by which the pool of effector T cells against a viral infection can quickly enlarge. Our data show that virus-specific CD8+ cytotoxic T lymphocytes (CTL) can transfer their T cell receptors (TCR) to recipient CTL of an unrelated specificity that, as a consequence, gain the antigen specificity of the donor T cell. This process occurs within minutes via membrane exchange and results in the recipient CTL acquiring the ability to recognize and eliminate cells targeted by the donor TCR, while still retaining the antigen specificity of its own TCR. Such receptor sharing allows rapid, proliferation-independent expansion of virus-specific T cell clones of low frequency and plays a highly significant antiviral role that can protect the host from an otherwise lethal infection. [ABSTRACT FROM AUTHOR]

Live viral vaccines elicit protective, long-lived humoral immunity, but the underlying mechanisms through which this occurs are not fully elucidated. Generation of affinity matured, long-lived protective antibody responses involve close interactions between T follicular helper (TFH) cells, germinal center (GC) B cells, and T follicular regulatory (TFR) cells. We postulated that escalating concentrations of antigens from replicating viruses or live vaccines, spread through the hematogenous route, are essential for the induction and maintenance of long-lived protective antibody responses. Using replicating and poorly replicating or nonreplicating orthopox and influenza A viruses, we show that the magnitude of TFH cell, GC B cell, and neutralizing antibody responses is directly related to virus replicative capacity. Further, we have identified that both lymphoid and circulating TFH:TFR cell ratios during the peak GC response can be used as an early predictor of protective, long-lived antibody response induction. Finally, administration of poorly or nonreplicating viruses to allow hematogenous spread generates significantly stronger TFH:TFR ratios and robust TFH, GC B cell and neutralizing antibody responses. [ABSTRACT FROM AUTHOR]