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1993 ; 84
(11
): 1181-9
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Suppression of anti-tumor CD4+ T cell responsiveness in the tumor-bearing state
and its recovery in in vitro culture free of tumor burden
#MMPMID7903964
Nagata T
; Zou JP
; Yamamoto N
; Ono S
; Fujiwara H
; Hamaoka T
Jpn J Cancer Res
1993[Nov]; 84
(11
): 1181-9
PMID7903964
show ga
We investigated whether the responsiveness of anti-tumor CD4+ T cells suppressed
in the tumor-bearing state is reversed in conditions free of tumor burden. Spleen
cells from BALB/c mice bearing a syngeneic tumor (CSA1M) 1-3 wk after inoculation
with CSA1M cells produced interleukin-2 (IL-2) and IL-4 upon in vitro culture
without addition of exogenous tumor antigens. This lymphokine production was
achieved through collaboration between anti-CSA1M CD4+ T cells and
antigen-presenting cells (APC) that had been pulsed with CSA1M tumor antigens in
vivo in the tumor-bearing state. However, spleen cells from late (8-10 wk)
tumor-bearing stages produced reduced levels of lymphokine production despite the
presence of comparable proportions of CD4+ T cells. Because APC in these cell
populations exhibited enhanced capacities to present tumor antigens, reduced
responsiveness was ascribed to the dysfunction of CD4+ T cells themselves. When
spleen cells from early tumor-bearing mice were preincubated for 1-2 days and
recultured in fresh medium, the magnitude of lymphokine production by these cells
was not changed. In contrast, the same protocol of preincubation and reculture
for cells from late tumor-bearing mice resulted in the recovery of anti-tumor
lymphokine-producing capacity. The recovered capacity was comparable to or
slightly higher than that expressed by cells from early tumor-bearing stages.
Since the CD4+ T cell content did not significantly differ before and after
preincubation, enhanced lymphokine production was due to the recovered
responsiveness of anti-tumor CD4+ helper T cells. The recovery of anti-tumor
responsiveness was also induced in vivo by tumor removal at the late
tumor-bearing stage: spleen cells from mice 2-4 wk after tumor resection
efficiently produced IL-2 and IL-4. These results indicate that the
immunodysfunction of anti-tumor CD4+ T cells induced in the tumor-bearing state
is reversible because release from tumor burden either by preincubation in vitro
or by tumor removal in vivo results in almost complete recovery of the potent
anti-tumor responsiveness initially expressed.