Histocompatibility antigen-activated cytotoxic T lymphocytes. II. Estimates of the frequency and specificity of precursors.

Abstract

Using limiting dilutions of responding cells in mouse mixed leukocyte cultures, we obtained direct estimates of the minimum frequency of precursors of cytotoxic T lymphocytes (CTL.P) for a variety of antigens. Depending on the strain combination, there were as many as 4-15 CTL.P reactive to DBA/2 among 10(4) lymph node cells. Taking into account that only 5-10% of peripheral T lymphocytes have the potential to develop into cytotoxic T lymphocytes (CTLs) (6), this implies that at least 1-2% of all CTL.P are responsive to any given H-2 haplotype difference. Precursors of cytotoxic cells thus have the same high frequency of cells reactive to alloantigens of the major histocompatibility complex as found among proliferating cells in graft-vs.-host reactions and mixed lymphocyte interactions. The frequencies of CTL.P reactive to xenoantigens (rat) or trinitrophenyl-modified self were less than half the frequency of alloreactive CTL.P. A minority of the CTL.P specific for one H-2 haplotype were also reactive to a third party H-2 haplotype, presumably on the basis of recognition of shared determinants. By dilution of sensitized cells from single microcultures, it was shown that a single CTL.P undergoes a minimum of three to four cell divisions and generates at least 8-16 CTLs after antigenic activation.

Frequency of Murine Cytotoxic T Cell Precursors Reactive to Plasma Cell Tumour‐associated Antigens as Compared to Major Histocompatibility Antigens

“…The results shown are also in agreement with those of others which have shown that there is a higher CTL-P frequency for an MHC plus a non-MHC alloantigenic difference than for MHC alloantigens alone (Lindahl and Wilson, 1977).…”

“…of the background for a particular target cell, and then scoring the wells assayed with that target positive if the counts in the supernatant were greater than the background count + 3 x S.D. of the background, as advocated by Lindahl and Wilson (1977). The percentage of negative wells for each responder number was then determined and plotted on a logarithmic scale against the responder number on an arithmetic scale, for analysis by Poisson distribution as described in detail previously (Burton et al, 1980).…”

At the crossroads between tolerance and aggression

“…16,20 Accordingly, a fetal T cell to a given alloantigen when compared with individual autoantigens. 41 Our findings suggested a potential model for how tolerance could be achieved to antigens perceived by the fetal immune system in utero. 42 We and others showed that human fetal lymphoid tissues, and some non-lymphoid tissues, contained small but detectable levels of maternal cells.…”

Clonal analysis of the effect of iron on human cytotoxic and proliferating T lymphocytes

“…Limiting dilution techniques have now been developed whieh permit an analysis ofthe various T lymphoeyte subsets (10)(11)(12)(13). Previous investigations using limit ing dilution techniques in miee have shown that iron: reduces the response by allospecifie eytotoxie T lymphoetyes (14,15); it reduces the ability of muritie CD8" T lymphoeyles to proliferate: it also reduces the proliferative response of human CD4 ^ memory T lymphoeytes to tetanus toxoid antigen (16).…”