Sequential antigen‐specific growth of T cells in the T zones and follicles in response to pigeon cytochrome c

Abstract

The sites of accumulation and growth of antigen-specific T cells was assessed during the V alpha 11/V beta 3 T cell receptor-restricted response of IEk+ mice to pigeon cytochrome c. In the T zone, the response was early but transient; V alpha 11/V beta 3+ T cell numbers fell to background levels as germinal centers developed. The follicles were a major site of specific T cell growth, but V alpha 11/V beta 3+ T cells were not obvious in foci of extrafollicular B cell growth in the red pulp. As germinal centers waned, V alpha 11/V beta 3+ T cells in the T zones again rose above background levels and some persisted in the follicles. After the initial stage of T cell priming, specific T cell growth seems to occur where specific interaction can occur with B cells that are presenting processed antigen.

Role of Ox40 Signals in Coordinating Cd4 T Cell Selection, Migration, and Cytokine Differentiation in T Helper (Th)1 and Th2 Cells

“…The CD4 T cell response to pigeon cytochrome C model is well characterized and would provide an excellent system in which to test this possible mechanism 11 23. It would be very interesting to establish whether the impaired CD4 T cell memory reported here in OX40L-deficient mice was linked with a failure to efficiently expand high-affinity CD4 T cells and export them to B follicles.…”

“…In contrast, constitutive expression of OX40L on DCs 3 is associated with the opposite phenotype, with increased numbers of activated/memory CD4 T cells 6. It seems likely that during normal CD4 T cell priming, the combination of costimulation through CD28 and OX40 is responsible for the rapid expansion of antigen-specific CD4 blasts that is observed in the T zone, peaking around day 7 11 12.…”

Recirculating CD4 memory T cells mount rapid secondary responses without major contributions from follicular CD4 effectors and B cells

“…In this response antigen-reactive CD4 T cells are prominent among Va11 + Vb3 + T cells [16], allowing the T cell response to be traced by following the number and distribution of Va11 + Vb3 + CD4 T cells. Although there are far fewer PCC-responsive CD4 T cells than superantigen-responsive Vb6 + cells, the pattern of recruitment, expansion, and survival of PCC-responsive cells is similar to that seen for superantigen-responsive cells following infection with MMTV(SW) (Fig.…”

“…As there is no stimulation from antigen-presenting cells in remote LN, the frequency of antigen-specific T cells will fall here from the earliest stages after immunization. Draining LN, by contrast, provide additional environments where antigen-dependent stimulation is provided: follicles with germinal centers [16,41,42] containing follicular dendritic cells that hold long-term depots of antigen and also B cells that provide cognate interactions.…”

“…It is unclear whether the responding CD4 T cell in this situation is a central memory T cell [16,17], or whether effector T cells, like the T cells that colonize follicles in LN responding to antigen, play a major role. Effector T cells in germinal centers select B cells that have undergone hypermutation [17,18] and these T cells can persist in follicles for months [19].…”