Functional analysis of mononuclear cells infiltrating into tumors. III. Soluble factors involved in the regulation of T lymphocyte infiltration into tumors.
We have analyzed the mechanisms controlling the accumulation of T lymphocytes in tumor tissues. Spleen cells, left or right popliteal lymph node cells, and tumor-infiltrating cells were obtained from tumor-inoculated rats and were cultured for 24 h. Culture supernatants were obtained and assessed for lymphocyte migration factor (LMF) activity with the use of a modified Boyden chamber. We found that tumor-infiltrating cells derived from T-9-sensitized rats produced LMF. Two waves of LMF production were observed. The first wave of LMF production was detected between 6 and 12 h (LMF-a) and the second wave of LMF production was detected between 4 and 6 days (LMF-4d and -6d) after tumor inoculation. The tumor-infiltrating cells consisted of heterogenous cell populations. We found that only tumor-infiltrating neutrophils of T-9-sensitized rats produced LMF-a. Five peaks of LMF (A through E) were detected upon fractionation of LMF-a using Mono Q anion exchange column chromatography. Peak D exhibited the strongest activity. The action of peak D was chemotactic, but not chemokinetic. The m.w. of peak D was 33,000 and 70,000. Only W3/25 (+) (helper/inducer) T cells were found to be sensitive to peak D. The production of LMF-a by purified tumor-infiltrating neutrophils in vitro is in agreement with the histologic observation that the infiltration of neutrophils precedes the appearance of W3/25 (+) T cells in tumor tissues of T-9-sensitized rats. It is thus likely that peak D of LMF-a is responsible for the infiltration of T lymphocytes into tumor tissues.
Yamaki
T
T
Department of Pathology, Sapporo Medical College, Japan.
Uede
T
T
Shijubo
N
N
Kikuchi
K
K
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002630:Chemotactic Factors / Q000096:biosynthesis; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002852:Chromatography, Ion Exchange; D005260:Female; D005910:Glioma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D019410:Interleukin-16; D016209:Interleukin-8; D008222:Lymphokines / Q000096:biosynthesis / Q000302:isolation & purification / Q000502:physiology*; D008223:Lymphoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000145:classification / Q000378:metabolism / Q000502:physiology*; D013953:Thymus Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D002630:Chemotactic Factors; D019410:Interleukin-16; D016209:Interleukin-8; D008222:Lymphokines